Through the Human Connectome Project (HCP) our understanding of the functional connectome of the healthy brain has been dramatically accelerated. Given the pressing public health need, we must increase our understanding of how connectome dysfunctions give rise to disordered mental states. Mental disorders arising from high levels of negative emotion or from the loss of positive emotional experience affect over 400 million people globally. Such states of disordered emotion cut across multiple diagnostic categories of mood and anxiety disorders and are compounded by accompanying disruptions in cognitive function. Not surprisingly, these forms of psychopathology are the leading cause of disability worldwide. The Research Domain Criteria (RDoC) initiative spearheaded by NIMH offers a framework for characterizing the relations among connectome dysfunctions, anchored in neural circuits and phenotypic profiles of behavior and self-reported symptoms. Here, we report on our Connectomes Related to Human Disease protocol for integrating an RDoC framework with HCP protocols to characterize connectome dysfunctions in disordered emotional states, and present quality control data from a representative sample of participants. We focus on three RDoC domains and constructs most relevant to depression and anxiety: 1) loss and acute threat within the Negative Valence System (NVS) domain; 2) reward valuation and responsiveness within the Positive Valence System (PVS) domain; and 3) working memory and cognitive control within the Cognitive System (CS) domain. For 29 healthy controls, we present preliminary imaging data: functional magnetic resonance imaging collected in the resting state and in tasks matching our constructs of interest ("Emotion", "Gambling" and "Continuous Performance" tasks), as well as diffusion-weighted imaging. All functional scans demonstrated good signal-to-noise ratio. Established neural networks were robustly identified in the resting state condition by independent component analysis. Processing of negative emotional faces significantly activated the bilateral dorsolateral prefrontal and occipital cortices, fusiform gyrus and amygdalae. Reward elicited a response in the bilateral dorsolateral prefrontal, parietal and occipital cortices, and in the striatum. Working memory was associated with activation in the dorsolateral prefrontal, parietal, motor, temporal and insular cortices, in the striatum and cerebellum. Diffusion tractography showed consistent profiles of fractional anisotropy along known white matter tracts. We also show that results are comparable to those in a matched sample from the HCP Healthy Young Adult data release. These preliminary data provide the foundation for acquisition of 250 subjects who are experiencing disordered emotional states. When complete, these data will be used to develop a neurobiological model that maps connectome dysfunctions to specific behaviors and symptoms.

中文翻译：

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情绪紊乱状态的人类连接组项目：青年焦虑和抑郁大脑连接研究领域标准研究的协议和基本原理

通过人类连接组计划 (HCP)，我们对健康大脑功能连接组的理解得到了显着加速。鉴于紧迫的公共卫生需求，我们必须加深对连接组功能障碍如何导致精神状态紊乱的理解。由高度消极情绪或积极情绪体验丧失引起的精神障碍影响着全球 4 亿多人。这种情绪紊乱的状态跨越了多种情绪障碍和焦虑障碍的诊断类别，并伴随着认知功能的破坏而变得更加复杂。毫不奇怪，这些形式的精神病理学是全世界残疾的主要原因。由 NIMH 牵头的研究领域标准 (RDoC) 倡议提供了一个框架，用于描述连接组功能障碍之间的关系，锚定在神经回路和行为表型概况和自我报告的症状中。在这里，我们报告了我们的与人类疾病相关的连接组协议，用于将 RDoC 框架与 HCP 协议集成在一起，以表征情绪紊乱状态下的连接组功能障碍，并提供来自代表性参与者样本的质量控制数据。我们专注于三个与抑郁和焦虑最相关的 RDoC 域和结构：1) 负价系统 (NVS) 域内的损失和急性威胁；2) 正价系统 (PVS) 领域内的奖励评估和​​响应；3) 认知系统 (CS) 领域内的工作记忆和认知控制。对于 29 名健康对照者，我们提供了初步成像数据：在静息状态和匹配我们感兴趣的结构（“情绪”、“赌博”和“持续表现”任务）的任务中收集的功能磁共振成像，以及扩散加权成像。所有功能扫描都显示出良好的信噪比。已建立的神经网络在静息状态条件下通过独立成分分析得到稳健识别。负面情绪面孔的处理显着激活了双侧背外侧前额叶和枕叶皮质、梭状回和杏仁核。奖励在双侧背外侧前额叶、顶叶和枕叶皮质以及纹状体中引起反应。工作记忆与背外侧前额叶、顶叶、纹状体和小脑中的运动、颞叶和岛叶皮质。扩散纤维束成像显示沿着已知的白质纤维束的分数各向异性的一致轮廓。我们还表明，结果与 HCP 健康青年数据发布的匹配样本中的结果相当。这些初步数据为获取 250 名情绪失调的受试者提供了基础。完成后，这些数据将用于开发神经生物学模型，将连接组功能障碍映射到特定的行为和症状。这些初步数据为获取 250 名情绪失调的受试者提供了基础。完成后，这些数据将用于开发神经生物学模型，将连接组功能障碍映射到特定的行为和症状。这些初步数据为获取 250 名情绪失调的受试者提供了基础。完成后，这些数据将用于开发神经生物学模型，将连接组功能障碍映射到特定的行为和症状。